Opiates are a class of alkaloids produced by plants of the poppy family. The most common opiates produced by the poppy plants are morphine and codeine. These opiates have been used for centuries to prevent pain but their continual use leads to addiction. Synthetic analogues of morphine also exhibit the narcotic and addictive properties of the natural opiates and include heroin (diacetylmorphine), hydromorphone, hydrocodone, levorphanol, oxycodone and oxymorphone. The illicit use of opiates, particularly heroin and morphine, has resulted in a medical need for antibodies and diagnostics to rapidly detect the opiate metabolites in order to monitor and treat opiate addiction.
The preparation of antibodies to the class of opiates and opiate metabolites requires the synthesis of an opiate derivative in order to covalently attach the derivative to an antigenic polypeptide or protein. In addition, the opiate derivative is covalently attached to various polypeptides, proteins or labels for use in screening antibodies and in the immunoassay process. The opiate derivative should mimic the structure of the opiate metabolite sought to be measured. Therefore, the selection and synthesis of the types of opiate derivatives for covalent attachment to proteins, polypeptides or labels is critical. In addition, the opiate derivatives need to be stable to hydrolysis in an aqueous solution.
Opiate compounds and conjugates for immunization and immunoassay have been described in U.S. Pat. Nos. 3,709,868, 3,852,157, 3,867,366, 3,884,898, 4,022,878, and in Science 176, 1143 (1972), and Science 178, 647 (1972).